Project Summary The DRCR.net is a research network dedicated to facilitating multicenter clinical research of diabetic retinopathy (DR), age-related macular degeneration (AMD), hereditary retinal degenerations and other retinal diseases. The Network?s mission is to identify, create, conduct, analyze and disseminate high quality clinical studies that lead to a better understanding of retinal diseases, advance their treatment, and improve the lives of individuals with retinal pathology. The DRCR.net operates through a highly collaborative network comprised of a Coordinating Center, two Network Chairs, over 100 clinical sites, and other central resource groups such as image reading centers. This standing infrastructure, along with the substantial clinical and scientific expertise of its investigators, allows the Network to be highly efficient and effective in the design, implementation and reporting of large-scale, ophthalmic clinical studies of major public health priority. In the United States alone, it is estimated that nearly 20 million Americans are affected by retinal pathology from DR, AMD, retinal vein occlusion, myopic choroidal neovascularization, retinopathy of prematurity, or inherited retinal diseases. The US economic burden from retinal disorders totals as much as $8.7 billion per year. The DRCR.net is uniquely poised to make impactful and continuing contributions to the fight against vision loss from retinal diseases including DR and AMD. Since its inception in 2002, DRCR.net has successfully made numerous and substantial contributions to the improvement of visual outcomes in diabetic patients. DRCR.net studies have addressed efficacy of novel therapies, cost effectiveness, patient quality of life, novel methods of retinal imaging and multiple aspects of visual function with major direct impact on clinical care guidelines and practices worldwide. The uniqueness of the Network and its efficiencies of scale allow the performance of protocols using money from the NIH, industry, and foundations. These protocols often involve trials that would not be done by industry and would not be feasible with solely NIH funding. Such protocols have included comparative effectiveness studies, trials supportive of new indications for approved drugs, and studies testing new therapies. The major goals of the DRCR.net over the next 5 year period include 1) completing the 7 studies currently ongoing in the DRCR.net, 2) continuing to develop and implement protocols in a rapid and efficient manner while maintaining absolute scientific rigor and integrity, 3) maintaining a transparent and open collaborative Network and 4) continuing to effectively disseminate trials results, treatment algorithms, and datasets to clinicians and other researchers. Given its previous accomplishments, robust organization, high visibility within the retinal community and strong enthusiasm of its investigators and personnel, the DRCR.net anticipates success in designing and implementing clinical studies over the next 5 year period that will substantially and positively impact our ability to preserve and improve vision in patients with retinal disease in the US and across the globe.